About That "First Gene-Edited Human Embryos" Story.....

BREAKING NEWS: The sky is not falling. Brave New World and GATTACA are not right around the corner. And the newest “designer baby” breakthrough is, at most, an interesting incremental step.

The last few days have seen enormous attention paid to an unpublished human embryo paper—one, quite possibly, as yet unread by anyone commenting on it. According to the MIT Technology Review, Shoukhrat Mitalipov of the Oregon Health Sciences University will soon publish a paper about his successful use of the hot DNA technology CRISPR—clustered regularly interspaced short palindromic repeats—to modify viable human embryos.

“According to people familiar with the scientific results,” Mitalipov edited “a large number of one-cell embryos.” Mitalipov and colleagues “are said to have convincingly shown” that they could avoid two problems encountered in other CRISPR experiments in editing embryos: off target effects, where CRISPR changes the wrong bits of DNA, and mosaicism, where CRISPR changes some cells but not all. The embryos were destroyed after “a few days” and were never intended to be transferred into a woman’s uterus for possible implantation and birth. Sperm from men carrying disease mutations was used to make the embryos, though Technology Review “could not determine which disease genes had been chosen for editing.” The story discusses legal bans on making babies using this method but ends with “Despite such barriers, the creation of a gene-edited person could be attempted at any moment, including by IVF clinics operating facilities in countries where there are no such legal restrictions.“

Mitalipov declined to comment because the paper was awaiting publication. It is not clear that the story’s author—or anyone commenting—actually read the paper.

So, a story, without great detail and using almost entirely anonymous sources, breaks about an unpublished research article. And at least some parts of Twitter break. What’s going on?

Let’s assume the story is true. What does it mean?

A bit, but, I’d argue, not much.

This is not the first time human embryos have been edited by CRISPR. That was done in China, in 2015 and in 2016, but both times with non-viable human embryos. It is not the first time (presumably—the story does not expressly say) viable human embryos have been edited by CRISPR. That was done at least once in China in early 2017. And it is certainly not the first time that mammalian embryos have been edited by CRISPR. It is the first time it has been done in the U.S. but the human embryos and the science won’t care about researchers’ nationalities.

What seems new and interesting is that Mitalipov had more success at modifying embryos—but how much more success? No numbers are given. He does seem to have used CRISPR at the fertilized egg or zygote stage, when the embryo has only one cell. That should reduce the mosaicism problem—with only one cell you’ll either modify all the cells or none of them, not just some of them. That result has not been published before in human embryos; I cannot tell whether it has been successfully done in non-human embryos.

But if the Technology Review article is fully accurate, this does not mean that designer babies are right around the corner or that genome editing in embryos is safe. The safety questions around using CRISPR and human embryos are enormous, in large part because the stakes—the health of human babies—are huge. Even if other labs replicate Mitalipov’s results and if the accuracy really is very high, the first few days of an embryo’s existence are only a tiny fraction of the time toward making a baby. A vast amount of work on genome-edited non-human embryos, ultimately brought to full term, and much more, and more thorough, work on ex vivo human embryos would need to be done to provide evidence of safety. The safety studies would likely take 10 to 15 years before FDA or other regulators would even consider allowing clinical trials. The Mitalipov research could mean that moment is 9 years and 10 months away instead of 10 years, but it is not close.

On February 14 of this year, the U.S. National Academy of Sciences (NAS) published a report on human genome editing. It carefully distinguished between 1) basic research in human genome editing, 2) the use of such editing to treat diseases in living people, and 3) its use to change the genomes of embryos in ways that could pass down to future generations (so-called “germline modifications). It argued that the first two should be relatively uncontroversial but that the last would require extensive discussion.

The Mitalipov paper is in the first category. The discussion around the paper has jumped to the third category. But we have plenty of time to have the necessary discussions of making CRISPRed babies. The NAS report was a good start on such discussions, as was a Nuffield Council report in the U.K. But much more discussion is needed before a final policy is made, discussion not just among experts but by legislators, regulators, and ordinary people. But we should take the time we have. Policies made in a rush, in response to a perceived crisis, are often bad policies. Nothing in the Mitalipov paper should lead us to rush. Making babies with genome edits (as opposed to making untransferred human embryos with such edits) is currently illegal in the U.S. Most scientifically advanced countries also make it illegal, either through safety regulations, like the FDA’s, or by frank statutory bans. What should the U.S. do? Keep calm, and think and discuss on.

But what of the story’s conclusion, that “the creation of a gene-edited person could be attempted at any moment”? Well, yes, an insanely reckless person could try that—if he, and a prospective mother, and physicians, and clinics, are willing to run the safety risks to the child as well as the political, malpractice, and legal risks to themselves. Will they? I doubt it. And if someone did, and one such child were born—and (one has to hope) were healthy—would it change the world? I think not. Widespread clinical use might change the world, not the occasional crazy outlier.

We have time. We don’t have unlimited time, so the discussions need to proceed. But not with a sense of crisis—in spite of many reactions to this as yet unpublished and unread paper.

The views expressed are those of the author(s) and are not necessarily those of Scientific American.

ABOUT THE AUTHOR(S)

Henry T. Greely

Henry T. Greely is Director of the Center for Law and the Biosciences and Professor (by courtesy) of Genetics, at the Stanford School of Medicine. He is the Chair of the Steering Committee of the Center for Biomedical Ethics, and Director of the Stanford Program in Neuroscience and Society.

Scientific American is part of Springer Nature, which owns or has commercial relations with thousands of scientific publications (many of them can be found at www.springernature.com/us). Scientific American maintains a strict policy of editorial independence in reporting developments in science to our readers.